GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network

Scott, Patricia M.; Bilodeau, Patricia S.; Zhdankina, Olga; Winistorfer, Stanley C.; Hauglund, Melissa J.; Allaman, Margaret M.; Kearney, William R.; Robertson, Andrew D.; Boman, Annette L.; Piper, Robert

doi:10.1038/ncb1107

Cited by 161 publications

(180 citation statements)

References 28 publications

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“…The known functions of ARF proteins and the ARD1 ARF domain might indicate an association with Golgi structure and lysosomes in processes related to vesicular transport. Relationships among ubiquitin, trans-Golgi network, and endosomal compartments have been reported (48,49). These studies demonstrated that Golgi-localized, gamma-ear-containing, ARFbinding (GGA) proteins bind ubiquitin through their GAT domains to accomplish protein sorting at the trans-Golgi network and transport toward endosomes.…”

Section: Discussionmentioning

confidence: 97%

E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1)

Vichi

Payne

Pacheco–Rodriguez

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Protein ubiquitinylation plays a key role in many important cellular processes. Ubiquitinylation requires the E1 ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and, frequently, a substrate-specific E3 ubiquitin-protein ligase. In one class of E3 ubiquitin ligases, the catalytic domain contains a zinc-binding RING finger motif. ARD1 (ADP-ribosylation factor domain protein 1), with a RING finger domain in the N-terminal region, two predicted B-Boxes, and a coiled-coil protein interaction motif immediately preceding an ADP-ribosylation factor domain at the C terminus, belongs to the TRIM (Tripartite motif) or RBCC (RING, B-Box, coiled-coil) family. The region containing the B-Boxes and the coiled-coil motif acts as a GTPase-activating protein for the ADPribosylation factor domain of ARD1. We report here that fulllength ARD1 or the RING finger domain (residues 1-110) produced polyubiquitinylated proteins in vitro in the presence of mammalian E1, an E2 enzyme (UbcH6 or UbcH5a, -5b, or -5c), ATP, and ubiquitin. Deletion of the RING region or point mutations within the RING sequence abolished ARD1 E3 ligase activity. All data are consistent with a potential function for ARD1 as an E3 ubiquitin ligase in cells.RBCC ͉ TRIM protein ͉ ARF ͉ ARF-GAP

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Section: Discussionmentioning

confidence: 97%

E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1)

Vichi

Payne

Pacheco–Rodriguez

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Mutation of leucine 280 in site 2 of the human Gga3 GAT domain results in a complete loss of interaction with mono-ubiquitin-agarose (28) or GST-ubiquitin (22), although a GST-Gga3-GAT fusion protein with this mutation demonstrated reduced but detectable binding to mono-and polyubiquitin by pulldown and surface plasmon resonance (23). Yeast Gga1 and Gga2 also have been shown to bind ubiquitin (22,27), but the ubiquitin-binding sites have not been mapped in the yeast Gga proteins. We introduced a mutation in the GAT domain of yeast Gga2 (L303A) that corresponds to the Leu-280 site 2 mutation of human Gga3 (Fig.…”

Section: Loss Of Ubiquitin Binding With Mutation Of a Site 2 Leucinementioning

confidence: 99%

“…The amino-terminal VHS domain of mammalian Ggas binds to an acidic di-leucine sorting signal defined by the consensus motif DXXLL, which is located in the cytosolic domain of cargo proteins; however, in yeast, cargo proteins do not contain this type of motif, and the residues of the VHS domain of human Ggas that bind this motif are not conserved (20,21). The GAT domain of human Gga3 also contains two binding sites for ubiquitin, and a number of conserved hydrophobic amino acid residues in the carboxylterminal half of the GAT domain have been shown to directly contribute to ubiquitin binding at the two sites (22)(23)(24)(25)(26)(27)(28).…”

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confidence: 99%

Gga2 Mediates Sequential Ubiquitin-independent and Ubiquitin-dependent Steps in the Trafficking of ARN1 from the trans-Golgi Network to the Vacuole

Deng¹,

Guo²,

Watson

et al. 2009

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, ARN1 encodes a transporter for the uptake of ferrichrome, an important nutritional source of iron. In the absence of ferrichrome, Arn1p is sorted directly from the trans-Golgi network (TGN) to the vacuolar lumen via the vacuolar protein-sorting pathway. Arn1p is mis-sorted to the plasma membrane in cells lacking Gga2p, a monomeric clathrin-adaptor protein involved in vesicular transport from the TGN. Although Ggas have been characterized as ubiquitin receptors, we show here that ubiquitin binding by Gga2 was not required for the TGN-to-endosome trafficking of Arn1, but it was required for subsequent sorting of Arn1 into the multivesicular body. In a ubiquitin-binding mutant of Gga2, Arn1p accumulated on the vacuolar membrane in a ubiquitinated form. The yeast epsins Ent3p and Ent4p were also involved in TGN-to-vacuole sorting of Arn1p. Amino-terminal sequences of Arn1p were required for vacuolar protein sorting, as mutation of ubiquitinatable lysine residues resulted in accumulation on the vacuolar membrane, and mutation of either a THN or YGL sequence resulted in mis-sorting to the plasma membrane. These studies suggest that Gga2 is involved in sorting at both the TGN and multivesicular body and that the first step can occur without ubiquitin binding.

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“…Experimental evidence is needed to determine whether the modified UIM motif of the Arabidopsis and rice VHS domain proteins is functional (see Supplementary material Table S1). Ubiquitin binding and delivery of cargo proteins to the putative plant ESCRT-machinery might also be mediated by proteins with a GAT (GGA and TOM1) domain, which has been shown to bind ubiquitin in a similar mode as the UIM and is necessary for the transport of monoubiquitinated cargo proteins to the MVB pathway [34][35][36]. The proximity of a VHS domain is necessary for efficient binding of ubiquitin to GAT domains.…”

mentioning

confidence: 99%

Exploring the ESCRTing machinery in eukaryotes

Winter

Hauser

2006

Trends in Plant Science

164

200

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The profile of protein sorting into multivesicular bodies (MVBs) has risen recently with the identification of three heteromeric complexes known as ESCRT-I,-II,-III (Endosomal Sorting Complex Required for Transport). Genetic analyses in yeast have identified up to 15 soluble class E VPS (vacuolar protein sorting) proteins that have been assigned to the ESCRT machinery and function in cargo recognition and sorting, complex assembly, vesicle formation and dissociation. Despite their functional importance in yeast and mammalian cells, little is known about their presence and function in other organisms including plants. We have made use of the fully sequenced genomes of Arabidopsis thaliana and Oryza sativa, Drosophila melanogaster and Caenorhabditis elegans to explore the identity, structural characteristics and phylogenetic relationships of proteins assigned to the ESCRT machinery.Multivesicular bodies (MVBs) are late endosomal organelles with up to several hundred interluminal vesicles that originate by invagination and budding of the limiting endosomal membrane (Figure 1) [1,2]. MVBs are also prevacuolar compartments involved in the retrograde endocytotic pathway where, upon fusion to vacuoles or lysosomes, the interluminal vesicles are released [3][4][5][6]. In yeast and mammals, MVBs are involved in sorting and degradation of transmembrane surface proteins as transporters (e.g. GAP1, STE6 and PDR5), receptors (e.g. EGFR, GHR, STE3 and STE2), in budding of viruses (e.g. HIV, MuLV and RSV) and in lipid partitioning [7,8]. However, MVBs are also central for sorting vacuolar proteins directly from the late Golgi to the anterograde and biosynthetic pathway ( Figure 1) [9]. Furthermore, MVBs operate in the exocytotic pathway and the secreted interluminal vesicles are known as exosomes (Figure 1) [10][11][12]. Thus, MVBs act as an intermediate station for cargo on the way to degradation, intracellular recycling and secretion ( Figure 1). Although MVBs have been described in plants, little is known about their biogenesis, cargos and function [2,4,[13][14][15][16]. These studies show that plant MVBs are prevacuolar compartments and are labeled by vacuolar sorting receptor (VSR) antibodies such as BP80 [5,17]. Plant MVBs are not only involved in the transport of proteins to lytic but also to protein-storage vacuoles. As plasmalemmasomes in tobacco, MVBs have been implicated in the internalization of arabinogalactanrich plasma membrane proteins that are sequestered within the vacuole [18] Upstream cargo recognition and sorting system of the ESCRT machineryThe entry of membrane proteins into the MVB pathway starts with the binding of monoubiquitinated cargos to the outer endosomal membrane and the recruitment of the ESCRT-I complex. This membrane association is mediated by ubiquitin-binding proteins that contain one or two UIMs or a GAT domain in combination with protein domains that had been implicated in binding to membranes such as the phosphatidylinositol-3 phosphate (PI3P) binding FYVE finger domain (Figure...

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GGA proteins bind ubiquitin to facilitate sorting at the trans-Golgi network

Cited by 161 publications

References 28 publications

E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1)

E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1)

Gga2 Mediates Sequential Ubiquitin-independent and Ubiquitin-dependent Steps in the Trafficking of ARN1 from the trans-Golgi Network to the Vacuole

Exploring the ESCRTing machinery in eukaryotes

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